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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 28910

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Prof. Dr. Cosimo Sperti

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Department of Surgery, Oncology and Gastroenterology-DISCOG, University of Padua, Padua, Italy
Interests: chronic pancreatitis; cystic tumors; endocrine tumors; pancreatectomy; pancreatic neoplasms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pancreatic cancer is the fourth leading of cancer death in Western countries, and is going to become the second cause of gastrointestinal cancer death in the next years. Surgery and adjuvant therapy remains the standard treatment, but the recurrence rate is still high. Multimodality treatment, that is, neoadjuvant therapy and combination of chemotherapy, radiotherapy, immunotherapy, and surgery, appears essential in order to obtain better results, but definitive conclusions are lacking. There is a need for a better understanding of genetic alterations, clarifying the role of new biomarkers for precursor and invasive tumors, the identification of prognostic factors (i.e., nutritional, immunological, and surgical complications), and the management of recurrent cancer for patient’s tailored therapy. Furthermore, neuroendocrine tumors are increasingly recognized in clinical practice, and they include a variety of neoplasms with a different biological behaviour and treatment. In particular, the management of small non-functioning tumors is still controversial, while the treatment of advanced disease requires novel research strategies. The aim of this Special Issue is to focus on the results and problems of multimodality therapy for resectable and locally advanced pancreatic tumors, the search of prognostic factors for early and late outcomes after therapy, and the evaluation of novel strategies for individualized treatment. We are inviting relevant original research, systematic reviews, meta-analyses, and short communications covering the above-mentioned topics.

Prof. Cosimo Sperti
Guest Editor

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Keywords

Pancreatic cancer
Pancreatic neuroendocrine tumor
Multimodality therapy
Neoadjuvant therapy
Nutrition and cancer
Inflammation and cancer
Surgical complications and survival
Recurrent cancer
Radiotherapy
Immunotherapy

Related Special Issue

Recent Advances in Pancreatic Neoplasms: Part II in Journal of Clinical Medicine (4 articles)

Published Papers (14 papers)

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Editorial

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4 pages, 201 KiB

Open AccessEditorial

Recent Advances in Pancreatic Neoplasms

by Cosimo Sperti, Simone Serafini and Lucia Moletta

J. Clin. Med. 2021, 10(20), 4724; https://doi.org/10.3390/jcm10204724 - 14 Oct 2021

Viewed by 984

Abstract

Pancreatic neoplasms, both primary and secondary, include different pathological entities with variable biological behavior and, consequently, different treatment modalities [...] Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

Research

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12 pages, 2042 KiB

Open AccessArticle

Rate of Post-Operative Pancreatic Fistula after Robotic-Assisted Pancreaticoduodenectomy with Pancreato-Jejunostomy versus Pancreato-Gastrostomy: A Retrospective Case Matched Comparative Study

by Marco V. Marino, Adrian Kah Heng Chiow, Antonello Mirabella, Gianpaolo Vaccarella and Andrzej L. Komorowski

J. Clin. Med. 2021, 10(10), 2181; https://doi.org/10.3390/jcm10102181 - 18 May 2021

Cited by 4 | Viewed by 1513

Abstract

Background: Different techniques of pancreatic anastomosis have been described, with inconclusive results in terms of pancreatic fistula reduction. Studies comparing robotic pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) are scarcely reported. Methods: The present study analyzes the outcomes of two case-matched groups of patients who underwent PG (n = 20) or PJ (n = 40) after pancreaticoduodenectomy. The primary aim was to compare the rate of post-operative pancreatic fistula. Results: Operative time (375 vs. 315 min, p = 0.34), estimated blood loss (270 vs. 295 mL, p = 0.44), and rate of clinically relevant post-operative pancreatic fistula (12.5% vs. 10%, p = 0.82) were similar between the two groups. PJ was associated with a higher rate of intra-abdominal collections (7.5% vs. 0%, p = 0.002), but lower post-pancreatectomy hemorrhage (2.5% vs. 10%, p = 0.003). PG was associated with a lower rate of post-operative pancreatic fistula (POPF) (33.3% vs. 50%, p = 0.003) in the high-risk group of patients. Conclusions: The outcomes of post-operative pancreatic fistula are comparable between the two reconstruction techniques. PG may have a lower incidence of POPF in patients with high-risk of pancreatic fistula. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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12 pages, 1276 KiB

Open AccessArticle

The Ratio of C-Reactive Protein to Albumin Is an Independent Predictor of Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas

by Simone Serafini, Alberto Friziero, Cosimo Sperti, Lorenzo Vallese, Andrea Grego, Alfredo Piangerelli, Amanda Belluzzi and Lucia Moletta

J. Clin. Med. 2021, 10(10), 2058; https://doi.org/10.3390/jcm10102058 - 11 May 2021

Cited by 9 | Viewed by 1730

Abstract

There is growing evidence to indicate that inflammatory reactions are involved in cancer progression. The aim of this study is to assess the significance of systemic inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the ratio of C-reactive protein to albumin ratio (CAR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGps) in the diagnosis and prognosis of malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Data were obtained from a retrospective analysis of patients who underwent pancreatic resection for IPMNs from January 2005 to December 2015. Univariate and multivariate analyses were performed, considering preoperative inflammatory biomarkers, clinicopathological variables, and imaging features. Eighty-three patients with histologically proven IPMNs of the pancreas were included in the study, 37 cases of low-grade or intermediate dysplasia and 46 cases of high-grade dysplasia (HGD) or invasive carcinoma. Univariate analysis showed that obstructive jaundice (p = 0.02) and a CAR of >0.083 (p = 0.001) were predictors of malignancy. On multivariate analysis, only the CAR was a statistically significant independent predictor of HGD or invasive carcinoma in pancreatic IPMNs, identifying a subgroup of patients with a poor prognosis. Combining the CAR with patients’ imaging findings, clinical features and tumor markers can be useful in the clinical management of IPMNs. Their value should be tested in prospective studies. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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11 pages, 526 KiB

Open AccessArticle

Association between Low-Grade Chemotherapy-Induced Peripheral Neuropathy (CINP) and Survival in Patients with Metastatic Adenocarcinoma of the Pancreas

by Martina Catalano, Giuseppe Aprile, Monica Ramello, Raffaele Conca, Roberto Petrioli and Giandomenico Roviello

J. Clin. Med. 2021, 10(9), 1846; https://doi.org/10.3390/jcm10091846 - 23 Apr 2021

Cited by 4 | Viewed by 1715

Abstract

The combination of nab-paclitaxel and gemcitabine demonstrated greater efficacy than gemcitabine alone but resulted in higher rates of chemotherapy-induced peripheral neuropathy (CINP) in patients with metastatic pancreatic cancer (mPC). We aimed to evaluate the correlation between the development of treatment-related peripheral neuropathy and the efficacy of nab-P/Gem combination in these patients. mPC patients treated with nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² as a first-line therapy were included. Treatment-related adverse events, mainly peripheral neuropathy, were categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02. Efficacy outcomes, including overall survival (OS), progression-free survival (PSF), and disease control rate (DCR), were estimated by the Kaplan–Meier model. A total of 153 patients were analyzed; of these, 47 patients (30.7%) developed grade 1–2 neuropathy. PFS was 7 months (95% CI (6–7 months)) for patients with grade 1–2 neuropathy and 6 months (95% CI (5–6 months)) for patients without peripheral neuropathy (p = 0.42). Median OS was 13 months (95% CI (10–18 months)) and 10 months (95% CI (8–13 months)) in patients with and without peripheral neuropathy, respectively (p = 0.04). DCR was achieved by 83% of patients with grade 1–2 neuropathy and by 58% of patients without neuropathy (p = 0.03). In the multivariate analysis, grade 1–2 neuropathy was independently associated with OS (HR 0.65; 95% CI, 0.45–0.98; p = 0.03). nab-P/Gem represents an optimal first-line treatment for mPC patients. Among possible treatment-related adverse events, peripheral neuropathy is the most frequent, with different grades and incidence. Our study suggests that patients experiencing CINP may have a more favorable outcome, with a higher disease control rate and prolonged median survival compared to those without neuropathy. Full article

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6 pages, 437 KiB

Open AccessArticle

Association of Neutrophil, Platelet, and Lymphocyte Ratios with the Prognosis in Unresectable and Metastatic Pancreatic Cancer

by Jessica Allen, Colin Cernik, Suhaib Bajwa, Raed Al-Rajabi, Anwaar Saeed, Joaquina Baranda, Stephen Williamson, Weijing Sun and Anup Kasi

J. Clin. Med. 2020, 9(10), 3283; https://doi.org/10.3390/jcm9103283 - 13 Oct 2020

Cited by 10 | Viewed by 1785

Abstract

We examined the relationship between the daily rate of change of cancer antigen 19-9 (CA19-9) over the first 90 days of treatment (DRC90) and the pretreatment levels of neutrophils, lymphocytes, and platelets with the overall survival (OS) and progression-free survival (PFS) in patients with stage IV pancreatic ductal adenocarcinoma (PDA) who received chemotherapy. We retrospectively evaluated 102 locally advanced and metastatic PDA patients treated at the University of Kansas Cancer Center (KUCC) between January 2011 and September 2019. We compared the ratio of the pretreatment absolute neutrophil count to the pretreatment absolute lymphocyte count (NLR) and the ratio between the pretreatment platelet count to the pretreatment absolute lymphocyte count (PLR) with the OS and PFS. We compared the DRC90 to the OS and PFS. The ratios were analyzed using the log-rank trend test using the mean of the NLR, PLR, and DRC90 as the threshold for two groups within each variable. Patients with ≥mean NLR (4.6 K/µL) had a significantly lower OS (p = 0.0444) and PFS (p = 0.0483) compared with patients below the mean. Patients with PLR ≥ mean (3.9 K/µL) did not have a significantly different OS (p = 0.507) or PFS (p = 0.643) compared with patients below the mean. Patients with DRC90 ≥ mean (−1%) did not have a significantly different OS (p = 0.342) or PFS (p = 0.313) compared with patients below the mean. Patients with NLR ≥ mean (4.6 K/µL) had a significantly lower OS and PFS compared with patients with NLR below the mean. This implies the possibility of NLR as a prognostic marker in PDA that could guide treatment approaches but still requires validation in a larger cohort. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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11 pages, 1687 KiB

Open AccessArticle

A Plea for Surgery in Pancreatic Metastases from Renal Cell Carcinoma: Indications and Outcome from a Multicenter Surgical Experience

by Anna Caterina Milanetto, Luca Morelli, Gregorio Di Franco, Alina David, Donata Campra, Paolo De Paolis and Claudio Pasquali

J. Clin. Med. 2020, 9(10), 3278; https://doi.org/10.3390/jcm9103278 - 13 Oct 2020

Cited by 10 | Viewed by 1723

Abstract

Background: Pancreatic metastases from renal-cell carcinoma (RCC-PMs) are rare. Surgery may play a role in improving overall (OS) and disease-free survival (DFS). Methods: Clinical-pathological features, surgery and follow-up data of patients with RCC-PMs operated on in three pancreatic surgical centers (2000–2019) were retrospectively evaluated. Results: Thirty-nine patients (21 male/18 female, averaging 65 years) were enrolled. RCC-PMs were metachronous in 36 patients (mean 94 months, up to 24 years after nephrectomy), multiple in 21 patients, and with a median size of 2.5 (range, 0.7–7.5) cm. All the patients underwent pancreatic surgery (33 standard resections, 6 limited resections). Fifteen patients had post-operative complications (morbidity 38.5%). The median DFS was 63 months, and 19 out of 36 patients showed a disease recurrence. The median OS was 134 months, and 13 out of 36 patients were alive with no evidence of disease. At univariate analysis, lymph node positivity (HR 5.1, 95% CI 1.5–18), multi-visceral resection (HR 3.4, 95% CI 1.1–10) and synchronous RCC-PMs (HR 13, 95% CI 3–55) were significantly associated with a short OS. Conclusion: Surgery may allow a DFS up to 17 years in more than one third of patients, even after limited resections. Splenectomy and lymph node dissection are not mandatory. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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12 pages, 707 KiB

Open AccessArticle

Effect of Flowable Thrombin-Containing Collagen-Based Hemostatic Matrix for Preventing Pancreatic Fistula after Pancreatectomy: A Randomized Clinical Trial

by Yejong Park, Jae Hyung Ko, Dae Ryong Kang, Jun Hyeok Lee, Dae Wook Hwang, Jae Hoon Lee, Woohyung Lee, Jaewoo Kwon, Si-Nae Park, Ki-Byung Song and Song Cheol Kim

J. Clin. Med. 2020, 9(10), 3085; https://doi.org/10.3390/jcm9103085 - 24 Sep 2020

Cited by 3 | Viewed by 3051

Abstract

Background: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy. Methods: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. Results: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453–207.870, p = 0.024). Conclusion: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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12 pages, 1588 KiB

Open AccessArticle

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

by Natalia Gablo, Karolina Trachtova, Vladimir Prochazka, Jan Hlavsa, Tomas Grolich, Igor Kiss, Josef Srovnal, Alona Rehulkova, Martin Lovecek, Pavel Skalicky, Ioana Berindan-Neagoe, Zdenek Kala and Ondrej Slaby

J. Clin. Med. 2020, 9(8), 2440; https://doi.org/10.3390/jcm9082440 - 30 Jul 2020

Cited by 15 | Viewed by 2286

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates. Full article

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12 pages, 2208 KiB

Open AccessArticle

Prognostic Implications of 18-FDG Positron Emission Tomography/Computed Tomography in Resectable Pancreatic Cancer

by Cosimo Sperti, Alberto Friziero, Simone Serafini, Sergio Bissoli, Alberto Ponzoni, Andrea Grego, Emanuele Grego and Lucia Moletta

J. Clin. Med. 2020, 9(7), 2169; https://doi.org/10.3390/jcm9072169 - 9 Jul 2020

Cited by 7 | Viewed by 1958

Abstract

There are currently no known preoperative factors for determining the prognosis in pancreatic cancer. The aim of this study was to examine the role of 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography (18-FDG-PET/CT) as a prognostic factor for patients with resectable pancreatic cancer. Data were obtained from a retrospective analysis of patients who had a preoperative PET scan and then underwent pancreatic resection from January 2007 to December 2015. The maximum standardized uptake value (SUVmax) of 18-FDG-PET/CT was calculated. Patients were divided into high (>3.65) and low (≤3.65) SUVmax groups, and compared in terms of their TNM classification (Union for International Cancer Contro classification), pathological grade, surgical treatment, state of resection margins, lymph node involvement, age, sex, diabetes and serum Carbohydrate Antigen 19-9 (CA 19-9) levels. The study involved 144 patients, 82 with high SUVmax pancreatic cancer and 62 with low SUVmax disease. The two groups’ disease-free and overall survival rates were significantly influenced by tumor stage, lymph node involvement, pathological grade, resection margins and SUVmax. Patients with an SUVmax ≤ 3.65 had a significantly better survival than those with SUVmax > 3.65 (p < 0.001). The same variables were independent predictors of survival on multivariate analysis. The SUVmax calculated with 18-FDG-PET/CT is an important prognostic factor for patients with pancreatic cancer, and may be useful in decisions concerning patients’ therapeutic management. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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10 pages, 931 KiB

Open AccessArticle

Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer

by Woohyung Lee, Yejong Park, Jae Woo Kwon, Eunsung Jun, Ki Byung Song, Jae Hoon Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo, Seo Young Park and Song Cheol Kim

J. Clin. Med. 2020, 9(5), 1477; https://doi.org/10.3390/jcm9051477 - 14 May 2020

Cited by 11 | Viewed by 1969

Abstract

Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC). Results: CA 19-9 concentrations of 37–1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092–0.748; p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093–0.739; p = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140–0.642; p = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences. Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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9 pages, 2158 KiB

Open AccessArticle

Serotonin-Secreting Neuroendocrine Tumours of the Pancreas

by Anna Caterina Milanetto, Matteo Fassan, Alina David and Claudio Pasquali

J. Clin. Med. 2020, 9(5), 1363; https://doi.org/10.3390/jcm9051363 - 6 May 2020

Cited by 6 | Viewed by 2517

Abstract

Background: Serotonin-secreting pancreatic neuroendocrine tumours (5-HT-secreting pNETs) are very rare, and characterised by high urinary 5-hydroxyindole-acetic acid (5-HIAA) levels (or high serum 5-HT levels). Methods: Patients with 5-HT-secreting pancreatic neoplasms observed in our unit (1986–2015) were included. Diagnosis was based on urinary 5-HIAA or serum 5-HT levels. Results: Seven patients were enrolled (4 M/3 F), with a median age of 64 (range 38–69) years. Two patients had a carcinoid syndrome. Serum 5-HT was elevated in four patients. Urinary 5-HIAA levels were positive in six patients. The median tumour size was 4.0 (range 2.5–10) cm. All patients showed liver metastases at diagnosis. None underwent resective surgery; lymph node/liver biopsies were taken. Six lesions were well-differentiated tumours and one a poorly differentiated carcinoma (Ki67 range 3.4–70%). All but one patient received chemotherapy. Four patients received somatostatin analogues; three patients underwent ablation of liver metastases. One patient is alive with disease 117 months after observation. All the others died from disease progression after a follow-up within 158 months. Conclusions: Primary 5-HT-secreting pNETs are mostly metastatic to the liver; patients are not amenable to resective surgery. Despite high 5-HIAA urinary levels, few patients present with carcinoid syndrome. A five-year survival rate of 42.9% may be achieved with multimodal treatment. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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21 pages, 3712 KiB

Open AccessArticle

The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer

by Weiyao Li, Javier Martinez-Useros, Nuria Garcia-Carbonero, Maria J. Fernandez-Aceñero, Alberto Orta, Luis Ortega-Medina, Sandra Garcia-Botella, Elia Perez-Aguirre, Luis Diez-Valladares, Angel Celdran and Jesús García-Foncillas

J. Clin. Med. 2020, 9(5), 1252; https://doi.org/10.3390/jcm9051252 - 26 Apr 2020

Cited by 10 | Viewed by 2832

Abstract

P-element-induced wimpy testis (PIWI) proteins have been described in several cancers. PIWIL1 and PIWIL2 have been recently evaluated in pancreatic cancer, and elevated expression of PIWIL2 conferred longer survival to patients. However, PIWIL3’s and PIWIL4’s role in carcinogenesis is rather controversial, and their clinical implication in pancreatic cancer has not yet been investigated. In the present study, we evaluated PIWIL1, PIWIL2, PIWIL3 and PIWIL4 expression in pancreatic cancer-derived cell lines and in one non-tumor cell line as healthy control. Here, we show a differential expression in tumor and non-tumor cell lines of PIWIL3 and PIWIL4. Subsequently, functional experiments with PIWIL3 and/or PIWIL4 knockdown revealed a decrease in the motility ratio of tumor and non-tumor cell lines through downregulation of mesenchymal factors in pro of epithelial factors. We also observed that PIWIL3 and/or PIWIL4 silencing impaired undifferentiated phenotype and enhanced drug toxicity in both tumor- and non-tumor-derived cell lines. Finally, PIWIL3 and PIWIL4 evaluation in human pancreatic cancer samples showed that patients with low levels of PIWIL4 protein expression presented poor prognosis. Therefore, PIWIL3 and PIWIL4 proteins may play crucial roles to keep pancreatic cell homeostasis not only in tumors but also in healthy tissues. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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Review

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Open AccessReview

The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis

by Elisa Sefora Pierobon, Lucia Moletta, Sandra Zampieri, Roberta Sartori, Alessandra Rosalba Brazzale, Gianpietro Zanchettin, Simone Serafini, Giovanni Capovilla, Michele Valmasoni, Stefano Merigliano and Cosimo Sperti

J. Clin. Med. 2021, 10(14), 3033; https://doi.org/10.3390/jcm10143033 - 7 Jul 2021

Cited by 23 | Viewed by 2182

Abstract

Low muscle mass is associated with reduced survival in patients with different cancer types. The interest in preoperative sarcopenia and pancreatic cancer has risen in the last decade as muscle mass loss seems to be associated with poorer survival, higher postoperative morbidity, and mortality. The aim of the present study was to review the literature to compare the impact of low muscle mass on the outcomes of patients undergoing surgery for pancreatic adenocarcinoma. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 10 articles were analyzed in detail and included in the meta-analysis. Data were retrieved on 2811 patients undergoing surgery for pancreatic cancer. Meta-analysis identified that patients with low muscle mass demonstrated a significantly reduced OS when compared to patients without alterations of the muscle mass (ROM 0.86; 95% CI: 0.81–0.91, p < 0.001), resulting in a 14% loss for the former. Meta-analysis failed to identify an increase in the postoperative complications and length of stay of patients with low muscle mass. Our analysis confirms the role of low muscle mass in influencing oncologic outcomes in pancreatic cancer. Its role on surgical outcomes remains to be established. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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11 pages, 564 KiB

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Repeated Pancreatectomy for Isolated Local Recurrence in the Remnant Pancreas Following Radical Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Pooled Analysis

by Munseok Choi, Na Won Kim, Ho Kyoung Hwang, Woo Jung Lee and Chang Moo Kang

J. Clin. Med. 2020, 9(12), 3945; https://doi.org/10.3390/jcm9123945 - 5 Dec 2020

Cited by 7 | Viewed by 1858

Abstract

The mainstream treatment for recurrent pancreatic cancer is potent chemotherapy or chemoradiotherapy. However, recent clinical investigations have suggested a potential oncologic role of local resection of recurrent pancreatic cancer. This systemic review with a pooled analysis aimed to assess the potential role of local repeated pancreatectomy with respect to the survival outcomes for patients with recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. The PubMed database was searched, and 15 articles reporting on repeated pancreatectomy for local recurrence of PDAC in the remnant pancreas were identified. The pooled individual data were examined for the clinical outcomes of repeated pancreatectomy for recurrent PDAC. The survival analysis was performed using the Kaplan–Meier method. In the pooled analysis, the mean time interval from initial pancreatectomy to repeated pancreatectomy was 41.3 months (standard deviation (SD), 29.09 months). Completion total pancreatectomy was most commonly performed as repeated pancreatectomy (46 patients, 92.0%), and partial pancreatic resection was performed for only 4 (10.3%) patients. Twenty (40.9%) patients received postoperative chemotherapy following repeated pancreatectomy. The median overall survival was 60 months (95% confidential interval (CI): 45.99–74.01) after repeated pancreatectomy for isolated local recurrence in the remnant pancreas. Overall survival was markedly longer considering the timing of the initial pancreatectomy for pancreatic cancer (median, 107 months (95% CI: 80.37–133.62). The time interval between the initial and subsequent repeated pancreatectomy for pancreatic cancer was not associated with long-term oncologic outcomes (p = 0.254). Repeated pancreatectomy cannot completely replace adjuvant chemotherapy but should be considered for patients with isolated local recurrent PDAC in the remnant pancreas. Full article

(This article belongs to the Special Issue Recent Advances in Pancreatic Neoplasms)

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